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The role of the membrane-associated periodic skeleton in axons

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Abstract

The identification of the membrane periodic skeleton (MPS), composed of a periodic lattice of actin rings interconnected by spectrin tetramers, was enabled by the development of super-resolution microscopy, and brought a new exciting perspective to our view of neuronal biology. This exquisite cytoskeleton arrangement plays an important role on mechanisms regulating neuronal (dys)function. The MPS was initially thought to provide mainly for axonal mechanical stability. Since its discovery, the importance of the MPS in multiple aspects of neuronal biology has, however, emerged. These comprise its capacity to act as a signaling platform, regulate axon diameter—with important consequences on the efficiency of axonal transport and electrophysiological properties— participate in the assembly and function of the axon initial segment, and control axon microtubule stability. Recently, MPS disassembly has also surfaced as an early player in the course of axon degeneration. Here, we will discuss the current knowledge on the role of the MPS in axonal physiology and disease.

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Acknowledgements

In the case of data generated in our group, we are indebted to the Advanced Light Microscopy Facility at EMBL, Heidelberg, Germany. We apologize to researchers whose work could not be cited due to space constraints.

Funding

Work from the author’s group was funded by FEDER through the NORTE 2020 and Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of project NORTE-01-0145-FEDER-028623; PTDC/MED-NEU/28623/2017. Ana Rita Costa is funded by FCT (SFRH/BPD/114912/2016) and FSE (Programa Operacional Regional Norte).

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Ana Rita Costa and Monica Mendes Sousa wrote the manuscript.

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Correspondence to Monica Mendes Sousa.

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Costa, A.R., Sousa, M.M. The role of the membrane-associated periodic skeleton in axons. Cell. Mol. Life Sci. 78, 5371–5379 (2021). https://doi.org/10.1007/s00018-021-03867-x

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